Wells T N, Peitsch M C
Geneva Biomedical Research Institute, Switzerland.
J Leukoc Biol. 1997 May;61(5):545-50. doi: 10.1002/jlb.61.5.545.
The chemokine superfamily is a large group of more than 30 small proteins. Many of these were originally identified because of their role in the selective recruitment and activation of leukocytes during inflammation. More recently, some of the chemokine receptors and ligands have been implicated in the mechanism of viral infection for primate lentiviruses such as HIV-1. From the original identification of interleukin-8 (IL-8; the most studied member of the superfamily), the number of new family members has mushroomed over the last few years. Two events have dramatically altered the speed at which sequence information concerning novel chemokines has become available to the scientific community. First, many groups have been obtaining large amounts of sequence information from cDNA libraries by sequencing the clones at random, generating expressed sequence tags (ESTs). Although these ESTs are relatively short, typically less than 500 bases, this amount of sequence is usually sufficient to obtain the entire open reading frame for chemokines. Second, there has been a rapid growth in the use of the WorldWideWeb by bioinformatics groups. The Web was originally set up by the European Centre for Particle Physics (CERN) in Geneva as a method of transferring data between collaborating groups throughout the world. It has enabled biologists throughout the world to have almost instantaneous access both to the databases containing the EST sequences and to the automated tools that are required for searching such databases. With such methods we have been able to rapidly identify more than 10 new human chemokines from public domain databases. In addition to the known categories of chemokines, which are named C, CC, and CXC based on the spacings of N-terminal cysteine residues, we have been able to identify the first member of a novel chemokine subfamily, with a novel CXXXC cysteine spacing. Furthermore, we can subdivide the CC chemokines into monocyte chemotactic protein and macrophage inflammatory protein families based on their sequence identity levels, but also their clustering on the human genome, as identified on other Web sites. The rapid availability of all this data has reduced the amount of time spent on conventional gene identification, enabling us to move quickly on to trying to understand the biology and physiological relevance of these molecules. The novel chemokine sequences obtained and alignments with existing members of the superfamily are now contained within a Chemokine Information Source on an open access server, allowing further searching of chemokine sequences and increasing the availability of such data to the scientific community.
趋化因子超家族是一个由30多种小蛋白组成的大群体。其中许多最初是因其在炎症过程中白细胞的选择性募集和激活中的作用而被鉴定出来的。最近，一些趋化因子受体和配体与灵长类慢病毒（如HIV-1）的病毒感染机制有关。从白细胞介素-8（IL-8；超家族中研究最多的成员）最初被鉴定以来，新的家族成员数量在过去几年中迅速增加。有两件事极大地改变了科学界获取有关新型趋化因子序列信息的速度。首先，许多研究小组通过随机测序克隆从cDNA文库中获得了大量序列信息，产生了表达序列标签（EST）。虽然这些EST相对较短，通常少于500个碱基，但这些序列量通常足以获得趋化因子的整个开放阅读框。其次，生物信息学小组对万维网的使用迅速增加。万维网最初是由日内瓦的欧洲粒子物理中心（CERN）建立的，作为在全球合作小组之间传输数据的一种方法。它使世界各地的生物学家几乎能即时访问包含EST序列的数据库以及搜索此类数据库所需的自动化工具。通过这些方法，我们能够从公共领域数据库中迅速鉴定出10多种新的人类趋化因子。除了已知的趋化因子类别，即根据N端半胱氨酸残基的间距命名为C、CC和CXC的类别外，我们还能够鉴定出一个新型趋化因子亚家族的首个成员，其具有新型的CXXXC半胱氨酸间距。此外，我们可以根据CC趋化因子的序列同一性水平，以及它们在人类基因组上的聚类情况（如在其他网站上所确定的），将其细分为单核细胞趋化蛋白和巨噬细胞炎性蛋白家族。所有这些数据的迅速可得减少了在传统基因鉴定上花费的时间，使我们能够迅速转向试图理解这些分子的生物学和生理相关性。所获得的新型趋化因子序列以及与超家族现有成员的比对结果现在包含在一个开放获取服务器上的趋化因子信息源中，允许进一步搜索趋化因子序列，并增加此类数据对科学界的可得性。
